The role of the cystic fibrosis transmembrane conductance regulator in host protection against «Citrobacter rodentium» intestinal infection
Bibliographic record
Abstract
Cystic fibrosis (CF) is a fatal disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.Located in the membrane of various epithelial tissues and immune cells, CFTR plays a critical role in ion and fluid homeostasis.Although often associated with a respiratory phenotype, CF affects the gastrointestinal tract.Mouse models of CF display little lung pathology, but do possess an intestinal phenotype, characterized by obstruction, inflammation, and bacterial overgrowth.We have shown that F508 CF mice (Cftr tm1Eur ) are highly susceptible to intestinal infection with Citrobacter rodentium, with atypical localization and greater colonization of bacteria than WT mice.Notably, there are significantly more neutrophils in the small intestine of CF mice both at steady state and following infection.Despite this increase, we have shown that CF neutrophils are defective in reactive oxygen species (ROS) production and have decreased apoptosis compared to WT. CF mice also have altered Wnt signaling at steady state, with increased active -catenin in the intestinal stromal cell compartment.To determine the relative contributions of the Cftr-deficient myeloid and epithelial cell compartments to infection susceptibility, we generated mice with myeloid-specific Cftr inactivation.Myeloid-Cftr -/-mice were resistant to infection with no defects in myeloid cell ROS production or apoptosis.We are now generating mice with Cftr inactivation in the intestinal epithelium, to test the hypothesis that functional CFTR mediates its protection in an intestinal epithelial cell dependent manner.C. rodentium infection provides a model to study intestinal disease observed in CF patients.Furthermore, the lack of a robust mouse model of CF pulmonary disease renders our research important for the study of the role of CFTR at mucosal surfaces.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".